2007 Annual Report 1a.Objectives (from AD-416) 1) Characterize variation in the bovine prion gene complex in U.S. cattle populations. 2) Associate prion gene complex haplotypes with susceptibility to BSE. 1b.Approach (from AD-416) The project will take a population-based approach employing principles of genetic epidemiology. First, we will characterize polymorphisms and haplotype structure in the prion gene complex in U.S. and U.K. cattle populations. Then we will utilize this comprehensive knowledge of genetic variation to analyze BSE case-control sets for association with specific alleles. We hypothesize that alleles of the bovine prion gene complex are associated with increased susceptibility to BSE. 3.Progress Report This report documents research conducted under an Interagency Reimbursable Agreement between ARS and the USDA Cooperative State Research, Education, and Extension Service (CSREES), National Research Initiative Competitive Grants Program (NRICGP) Grant #2005-35212-15890. Additional details of research can be found in the report for the in-house CRIS 5438-32000-029-00D, Genetic and Biological Determinants of Respiratory Disease Sucptibility. Identification of polymorphisms in the bovine prion gene. Previously, a 25.2-kb genomic region encompassing the bovine prion gene (PRNP) was sequenced in panels representing the breadth of genetic diversity in U.S. beef and dairy cattle (n=192 individuals) resulting in identification of 388 total polymorphisms, 350 single nucleotide polymorphisms (SNP) and 38 insertion/deletions, of which 287 have not previously been reported. Sequencing of the rest of the prion gene complex, including the PRNP paralogs PRND (doppel) and PRNT is completed with an additional 330 polymorphisms identified. The PRND/PRNT region was found to be largely in linkage equilibrium with PRNP, indicating that alleles in these regions are not predicitve of one another.